Genetic Variant FAM110D:p.Pro186Arg (chr1-26161848-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024869.3(FAM110D):c.557C>G(p.Pro186Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000026 in 1,535,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

FAM110D
NM_024869.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19752029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM110D	NM_024869.3 link	c.557C>G	p.Pro186Arg	missense_variant	Exon 2 of 2	ENST00000374268.5	NP_079145.2	Q8TAY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM110D	ENST00000374268.5 link	c.557C>G	p.Pro186Arg	missense_variant	Exon 2 of 2	1	NM_024869.3	ENSP00000363386.3		Q8TAY7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000157

AC:

AN:

127034

Hom.:

AF XY:

0.0000143

AC XY:

AN XY:

69712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000846

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000217

AC:

AN:

1383434

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

682224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000854

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.557C>G (p.P186R) alteration is located in exon 2 (coding exon 1) of the FAM110D gene. This alteration results from a C to G substitution at nucleotide position 557, causing the proline (P) at amino acid position 186 to be replaced by an arginine (R). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0049

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.54

M_CAP

Benign

0.042

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.27

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Uncertain

0.016

Sift4G

Benign

0.30

Polyphen

0.92

Vest4

0.40

MutPred

0.17

Loss of loop (P = 0.0512);

MVP

0.068

MPC

2.3

ClinPred

0.64

GERP RS

4.6

Varity_R

0.42

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over