chr11-73407616-G-A

Variant names:

• chr11-73407616-G-A
• rs769799497
• NM_015159.3:c.623C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_015159.3(FAM168A):​c.623C>T​(p.Thr208Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,610,274 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 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: FAM168A NM_015159.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60
• Publications: 1 publications found

Genes affected

FAM168A (HGNC:28999): (family with sequence similarity 168 member A) Involved in positive regulation of base-excision repair. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256448 (HGNC:58441):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29473838).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015159.3. 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
	FAM168A	NM_015159.3	MANE Select	c.623C>T	p.Thr208Met	missense	Exon 7 of 8	NP_055974.1	Q92567-2
	FAM168A	NM_001286050.2		c.650C>T	p.Thr217Met	missense	Exon 8 of 9	NP_001272979.1	Q92567-1
	FAM168A	NM_001286051.2		c.305C>T	p.Thr102Met	missense	Exon 5 of 6	NP_001272980.1	Q92567-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM168A	ENST00000356467.5	TSL:1 MANE Select	c.623C>T	p.Thr208Met	missense	Exon 7 of 8	ENSP00000348852.4	Q92567-2
	FAM168A	ENST00000064778.8	TSL:1	c.650C>T	p.Thr217Met	missense	Exon 8 of 9	ENSP00000064778.4	Q92567-1
	FAM168A	ENST00000450446.6	TSL:1	c.305C>T	p.Thr102Met	missense	Exon 5 of 6	ENSP00000390501.2	Q92567-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000449 AC: 11 AN: 244962 AF XY: 0.0000601

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 31 AN: 1458078 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17 AN XY: 725418

African (AFR) AF: 0.00 AC: 0 AN: 33176

American (AMR) AF: 0.000136 AC: 6 AN: 44002

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39200

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1110612

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.000131 AC: 2 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000413 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	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	31
DANN	Benign	0.94
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PhyloP100		9.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.072	T
Polyphen		0.77	P
Vest4		0.63
MutPred		0.33		Loss of glycosylation at T217 (P = 0.0456)
MVP		0.18
MPC		1.5
ClinPred		0.46	T
GERP RS		4.8
Varity_R		0.25
gMVP		0.62
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs769799497; hg19: chr11-73118661;