6-26443624-C-A

Variant names:

• chr6-26443624-C-A
• NM_006994.5:c.50C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006994.5(BTN3A3):​c.50C>A​(p.Ser17Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S17F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTN3A3 NM_006994.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

BTN3A3 (HGNC:1140): (butyrophilin subfamily 3 member A3) The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A3) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).[supplied by OMIM, Nov 2010]

ENSG00000291336 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051380962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN3A3	NM_006994.5	c.50C>A	p.Ser17Tyr	missense_variant	Exon 3 of 11	ENST00000244519.7	NP_008925.1
BTN3A3	NM_197974.3	c.-60-17C>A		intron_variant	Intron 2 of 9		NP_932078.2
BTN3A3	NM_001242803.2	c.-41-333C>A		intron_variant	Intron 1 of 5		NP_001229732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN3A3	ENST00000244519.7	c.50C>A	p.Ser17Tyr	missense_variant	Exon 3 of 11	1	NM_006994.5	ENSP00000244519.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.1
DANN	Benign	0.63
DEOGEN2	Benign	0.034	.;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.60	T;T;T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.051	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	.;.;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.89	N;N;N;N
REVEL	Benign	0.053
Sift	Benign	1.0	T;T;T;T
Sift4G	Uncertain	0.055	T;D;T;T
Polyphen		0.013	.;.;B;.
Vest4		0.25
MutPred		0.53		Gain of catalytic residue at L12 (P = 0.0818);Gain of catalytic residue at L12 (P = 0.0818);Gain of catalytic residue at L12 (P = 0.0818);Gain of catalytic residue at L12 (P = 0.0818);
MVP		0.25
MPC		2.2
ClinPred		0.021	T
GERP RS		-1.7
Varity_R		0.052
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-26443852;