Genetic Variant SMIM5:p.Ser36Pro (chr17-75640307-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001162995.3(SMIM5):c.106T>C(p.Ser36Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,549,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SMIM5
NM_001162995.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Publications

0 publications found

Variant links:

Genes affected

SMIM5 (HGNC:40030): (small integral membrane protein 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM5 links:

RECQL5 (HGNC:9950): (RecQ like helicase 5) The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

RECQL5 Gene-Disease associations (from GenCC):

breast cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
coronary artery disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RECQL5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162995.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMIM5	NM_001162995.3	MANE Select	c.106T>C	p.Ser36Pro	missense	Exon 2 of 3	NP_001156467.1	Q71RC9
RECQL5	NM_004259.7	MANE Select	c.1230-8639A>G		intron	N/A	NP_004250.4
SMIM5	NR_028439.1		n.3713T>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMIM5	ENST00000375215.3	TSL:1 MANE Select	c.106T>C	p.Ser36Pro	missense	Exon 2 of 3	ENSP00000364363.3	Q71RC9
SMIM5	ENST00000537494.1	TSL:1	c.106T>C	p.Ser36Pro	missense	Exon 1 of 2	ENSP00000477017.1	Q71RC9
RECQL5	ENST00000317905.10	TSL:1 MANE Select	c.1230-8639A>G		intron	N/A	ENSP00000317636.5	O94762-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397774

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31502

American (AMR)

AF:

0.00

AC:

AN:

35338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25126

East Asian (EAS)

AF:

0.00

AC:

AN:

35660

South Asian (SAS)

AF:

0.00

AC:

AN:

79032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078262

Other (OTH)

AF:

0.00

AC:

AN:

57926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41378

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.69

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.80

PhyloP100

3.5

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.25

Sift

Benign

0.045

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.70

MutPred

0.41

Gain of loop (P = 0.0079)

MVP

0.072

ClinPred

0.97

GERP RS

5.1

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.73

gMVP

0.48

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over