dbSNP rs868633560: FAM110D:p.Pro242Gln (chr1-26162016-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024869.3(FAM110D):c.725C>A(p.Pro242Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P242R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM110D
NM_024869.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.247

Publications

0 publications found

Variant links:

Genes affected

FAM110D (HGNC:25860): (family with sequence similarity 110 member D)

FAM110D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038953304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024869.3. 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
	FAM110D	NM_024869.3	MANE Select	c.725C>A	p.Pro242Gln	missense	Exon 2 of 2	NP_079145.2	Q8TAY7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM110D	ENST00000374268.5	TSL:1 MANE Select	c.725C>A	p.Pro242Gln	missense	Exon 2 of 2	ENSP00000363386.3	Q8TAY7
FAM110D	ENST00000880266.1		c.725C>A	p.Pro242Gln	missense	Exon 3 of 3	ENSP00000550325.1
FAM110D	ENST00000880267.1		c.725C>A	p.Pro242Gln	missense	Exon 3 of 3	ENSP00000550326.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1085898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

516136

African (AFR)

AF:

0.00

AC:

AN:

22580

American (AMR)

AF:

0.00

AC:

AN:

8134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13936

East Asian (EAS)

AF:

0.00

AC:

AN:

26080

South Asian (SAS)

AF:

0.00

AC:

AN:

20772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

926342

Other (OTH)

AF:

0.00

AC:

AN:

43502

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151466

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

73958

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41338

American (AMR)

AF:

0.00

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67848

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.33

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-0.25

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.51

REVEL

Benign

0.023

Sift

Benign

0.21

Sift4G

Benign

0.071

Polyphen

0.0030

Vest4

0.067

MutPred

0.21

Loss of catalytic residue at P241 (P = 0.0131)

MVP

0.068

MPC

0.98

ClinPred

0.23

GERP RS

2.3

Varity_R

0.17

gMVP

0.23

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over