Genetic Variant NM_003004.3:c.659C>T (chr17-82322249-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003004.3(SECTM1):c.659C>T(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000908 in 1,607,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

SECTM1
NM_003004.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.610

Publications

2 publications found

Variant links:

Genes affected

SECTM1 (HGNC:10707): (secreted and transmembrane 1) This gene encodes a transmembrane and secreted protein with characteristics of a type 1a transmembrane protein. It is found in a perinuclear Golgi-like pattern and thought to be involved in hematopoietic and/or immune system processes. [provided by RefSeq, Jul 2008]

SECTM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014684588).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003004.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SECTM1	NM_003004.3	MANE Select	c.659C>T	p.Pro220Leu	missense	Exon 5 of 5	NP_002995.1	Q8WVN6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SECTM1	ENST00000269389.8	TSL:1 MANE Select	c.659C>T	p.Pro220Leu	missense	Exon 5 of 5	ENSP00000269389.3	Q8WVN6
SECTM1	ENST00000856789.1		c.659C>T	p.Pro220Leu	missense	Exon 5 of 5	ENSP00000526848.1
SECTM1	ENST00000856793.1		c.659C>T	p.Pro220Leu	missense	Exon 6 of 6	ENSP00000526852.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000101

AC:

AN:

247772

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000917

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000845

AC:

123

AN:

1455300

Hom.:

Cov.:

AF XY:

0.0000830

AC XY:

AN XY:

722868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33286

American (AMR)

AF:

0.00

AC:

AN:

44302

Ashkenazi Jewish (ASJ)

AF:

0.00154

AC:

AN:

25906

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39508

South Asian (SAS)

AF:

0.0000698

AC:

AN:

85976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000641

AC:

AN:

1107190

Other (OTH)

AF:

0.0000665

AC:

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000151

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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

Alfa

AF:

0.000328

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

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

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.012

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.51

M_CAP

Benign

0.0011

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.61

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

REVEL

Benign

0.041

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.017

Vest4

0.074

MVP

0.030

MPC

0.15

ClinPred

0.026

GERP RS

-1.6

Varity_R

0.042

gMVP

0.069

Mutation Taster

=100/0

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

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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