6-26413615-T-C

Position:

• chr6-26413615-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007048.6(BTN3A1):​c.1465T>C​(p.Ser489Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.681

Genes affected

BTN3A1 (HGNC:1138): (butyrophilin subfamily 3 member A1) 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., BNT3A1) 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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN3A1	NM_007048.6	c.1465T>C	p.Ser489Pro	missense_variant	10/10	ENST00000289361.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN3A1	ENST00000289361.11	c.1465T>C	p.Ser489Pro	missense_variant	10/10	1	NM_007048.6	P1
	ENST00000707189.1	n.1000-139572T>C		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-119090T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1465T>C (p.S489P) alteration is located in exon 10 (coding exon 9) of the BTN3A1 gene. This alteration results from a T to C substitution at nucleotide position 1465, causing the serine (S) at amino acid position 489 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.12	T;T
Sift4G	Benign	0.17	T;T
Polyphen		1.0	D;.
Vest4		0.31
MutPred		0.56		Loss of stability (P = 0.101);.;
MVP		0.73
MPC		0.18
ClinPred		0.26	T
GERP RS		0.69
Varity_R		0.47
gMVP		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs1338550281; hg19: chr6-26413843;