6-26443624-C-G

Variant names:

• chr6-26443624-C-G
• rs1028608102
• NM_006994.5:c.50C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006994.5(BTN3A3):​c.50C>G​(p.Ser17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: BTN3A3 NM_006994.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05925575).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006994.5. 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
	BTN3A3	NM_006994.5	MANE Select	c.50C>G	p.Ser17Cys	missense	Exon 3 of 11	NP_008925.1	O00478-1
	BTN3A3	NM_197974.3		c.-60-17C>G		intron	N/A	NP_932078.2	O00478-2
	BTN3A3	NM_001242803.2		c.-41-333C>G		intron	N/A	NP_001229732.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A3	ENST00000244519.7	TSL:1 MANE Select	c.50C>G	p.Ser17Cys	missense	Exon 3 of 11	ENSP00000244519.2	O00478-1
	BTN3A3	ENST00000949570.1		c.50C>G	p.Ser17Cys	missense	Exon 3 of 11	ENSP00000619629.1
	BTN3A3	ENST00000878509.1		c.50C>G	p.Ser17Cys	missense	Exon 2 of 10	ENSP00000548568.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.12
DANN	Benign	0.052
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00050	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.23	N
PhyloP100		-1.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.045
Sift	Benign	0.23	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.55		Gain of catalytic residue at L18 (P = 0.0143)
MVP		0.21
MPC		1.8
ClinPred		0.059	T
GERP RS		-1.7
Varity_R		0.047
gMVP		0.29
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1028608102; hg19: chr6-26443852; COSMIC: COSV105041133; COSMIC: COSV105041133;