NM_001732.3:c.544G>A

Variant names:

• chr6-26505041-G-A
• NM_001732.3:c.544G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001732.3(BTN1A1):​c.544G>A​(p.Gly182Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G182A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTN1A1 NM_001732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

Genes affected

BTN1A1 (HGNC:1135): (butyrophilin subfamily 1 member A1) Butyrophilin is the major protein associated with fat droplets in the milk. It is a member of the immunoglobulin superfamily. It may have a cell surface receptor function. The human butyrophilin gene is localized in the major histocompatibility complex (MHC) class I region of 6p and may have arisen relatively recently in evolution by the shuffling of exons between 2 ancestral gene families [provided by RefSeq, Jul 2008]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30007446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN1A1	NM_001732.3	c.544G>A	p.Gly182Arg	missense_variant	Exon 4 of 8	ENST00000684113.1	NP_001723.2
LOC107986583	XR_001744057.3	n.5890+16468C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN1A1	ENST00000684113.1	c.544G>A	p.Gly182Arg	missense_variant	Exon 4 of 8		NM_001732.3	ENSP00000507193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.544G>A (p.G182R) alteration is located in exon 3 (coding exon 3) of the BTN1A1 gene. This alteration results from a G to A substitution at nucleotide position 544, causing the glycine (G) at amino acid position 182 to be replaced by an arginine (R). 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	0.23
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		4.6
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.3	D;.
REVEL	Benign	0.14
Sift	Benign	0.079	T;.
Sift4G	Uncertain	0.058	T;T
Polyphen		0.73	P;.
Vest4		0.19
MutPred		0.50		Loss of ubiquitination at K184 (P = 0.02);Loss of ubiquitination at K184 (P = 0.02);
MVP		0.57
MPC		1.0
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.22
gMVP		0.48
Mutation Taster		=93/7	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

hg19: chr6-26505269; COSMIC: COSV55066692;