chr1-26161881-C-G

Variant names:

• chr1-26161881-C-G
• rs769436556
• NM_024869.3:c.590C>G

Variant summary

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

The NM_024869.3(FAM110D):​c.590C>G​(p.Ala197Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,469,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A197D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: FAM110D NM_024869.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.417
• Publications: 0 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.025046855).

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.590C>G	p.Ala197Gly	missense	Exon 2 of 2	NP_079145.2	Q8TAY7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM110D	ENST00000374268.5	TSL:1 MANE Select	c.590C>G	p.Ala197Gly	missense	Exon 2 of 2	ENSP00000363386.3	Q8TAY7
	FAM110D	ENST00000880266.1		c.590C>G	p.Ala197Gly	missense	Exon 3 of 3	ENSP00000550325.1
	FAM110D	ENST00000880267.1		c.590C>G	p.Ala197Gly	missense	Exon 3 of 3	ENSP00000550326.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 11 AN: 74144 AF XY: 0.0000946

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000390

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000210 AC: 277 AN: 1317100 Hom.: 0 Cov.: 32 AF XY: 0.000221 AC XY: 143 AN XY: 645710

African (AFR) AF: 0.00 AC: 0 AN: 26302

American (AMR) AF: 0.0000400 AC: 1 AN: 24990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22000

East Asian (EAS) AF: 0.00 AC: 0 AN: 30782

South Asian (SAS) AF: 0.00 AC: 0 AN: 70776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35042

Middle Eastern (MID) AF: 0.000231 AC: 1 AN: 4324

European-Non Finnish (NFE) AF: 0.000258 AC: 270 AN: 1048310

Other (OTH) AF: 0.0000916 AC: 5 AN: 54574

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000922 Hom.: 0

Bravo AF: 0.000170

ExAC AF: 0.0000921 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.62
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.42
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.045
Sift	Benign	0.37	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.091
MVP		0.093
MPC		1.1
ClinPred		0.0078	T
GERP RS		1.2
Varity_R		0.044
gMVP		0.12
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs769436556; hg19: chr1-26488372;