NM_001167676.2:c.227C>T

Variant names:

• chr1-32361784-G-A
• rs201679382
• NM_001167676.2:c.227C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001167676.2(FAM229A):​c.227C>T​(p.Ala76Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00062 in 1,324,002 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00065 (4 hom.)
• Consequence: FAM229A NM_001167676.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• Publications: 1 publications found

Genes affected

FAM229A (HGNC:44652): (family with sequence similarity 229 member A)

TSSK3 (HGNC:15473): (testis specific serine kinase 3) This gene encodes a kinase expressed exclusively in the testis that is thought to play a role in either germ cell differentiation or mature sperm function. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007926911).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167676.2. 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
	FAM229A	NM_001167676.2	MANE Select	c.227C>T	p.Ala76Val	missense	Exon 2 of 3	NP_001161148.1	H3BQW9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM229A	ENST00000432622.2	TSL:2 MANE Select	c.227C>T	p.Ala76Val	missense	Exon 2 of 3	ENSP00000455971.1	H3BQW9
	FAM229A	ENST00000416512.1	TSL:1	n.2440C>T		non_coding_transcript_exon	Exon 1 of 2
	FAM229A	ENST00000428500.1	TSL:2	c.41C>T	p.Ala14Val	missense	Exon 1 of 2	ENSP00000454338.1	H3BMD6

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00143 AC: 2 AN: 1400 AF XY: 0.00133

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: 0.00172

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000645 AC: 756 AN: 1171740 Hom.: 4 Cov.: 32 AF XY: 0.000707 AC XY: 398 AN XY: 563090

African (AFR) AF: 0.0000427 AC: 1 AN: 23400

American (AMR) AF: 0.00 AC: 0 AN: 8878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16052

East Asian (EAS) AF: 0.00 AC: 0 AN: 26840

South Asian (SAS) AF: 0.00356 AC: 159 AN: 44722

European-Finnish (FIN) AF: 0.000252 AC: 7 AN: 27824

Middle Eastern (MID) AF: 0.000434 AC: 2 AN: 4612

European-Non Finnish (NFE) AF: 0.000585 AC: 568 AN: 971370

Other (OTH) AF: 0.000395 AC: 19 AN: 48042

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152262 Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38 AN XY: 74454

African (AFR) AF: 0.000120 AC: 5 AN: 41566

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00310 AC: 15 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 67996

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00102 Hom.: 3

Bravo AF: 0.000355

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000185 AC: 2

Asia WGS AF: 0.00116 AC: 4 AN: 3468

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	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.061	T
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0079	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.6	D
Sift	Benign	0.087	T
Sift4G	Benign	0.46	T
Vest4		0.076
MVP		0.25
GERP RS		1.5
PromoterAI		0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.16
Mutation Taster		=91/9	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: rs201679382; hg19: chr1-32827385;