Genetic Variant NM_001145268.2:c.215G>C (chr7-102749422-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145268.2(FAM185A):c.215G>C(p.Ser72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,396,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

FAM185A
NM_001145268.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Publications

0 publications found

Variant links:

Genes affected

FAM185A (HGNC:22412): (family with sequence similarity 185 member A)

FAM185A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22874308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2 link	c.215G>C	p.Ser72Thr	missense_variant	Exon 1 of 8	ENST00000413034.3	NP_001138740.2	Q8N0U4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3 link	c.215G>C	p.Ser72Thr	missense_variant	Exon 1 of 8	5	NM_001145268.2	ENSP00000395340.2		Q8N0U4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000135

AC:

AN:

148538

AF XY:

0.0000252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000814

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000645

AC:

AN:

1396094

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

688540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31506

American (AMR)

AF:

0.000112

AC:

AN:

35656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25144

East Asian (EAS)

AF:

0.00

AC:

AN:

35718

South Asian (SAS)

AF:

0.00

AC:

AN:

79102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48546

Middle Eastern (MID)

AF:

0.000236

AC:

AN:

4236

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078394

Other (OTH)

AF:

0.0000173

AC:

AN:

57792

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.215G>C (p.S72T) alteration is located in exon 1 (coding exon 1) of the FAM185A gene. This alteration results from a G to C substitution at nucleotide position 215, causing the serine (S) at amino acid position 72 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0082

.;T

Eigen

Benign

0.026

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.6

.;M

PhyloP100

1.7

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.11

Sift

Benign

0.12

T;D

Sift4G

Benign

0.45

T;D

Polyphen

0.96

.;D

Vest4

0.29

MutPred

0.32

Loss of glycosylation at S72 (P = 0.0826);Loss of glycosylation at S72 (P = 0.0826);

MVP

0.040

ClinPred

0.72

GERP RS

1.2

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.12

gMVP

0.44

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_001145268.2:c.215G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over