rs781620493

Variant names:

• chr5-180993134-A-C
• rs781620493
• NM_197975.3:c.371A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_197975.3(BTNL3):​c.371A>C​(p.Glu124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,444,390 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000024 (8 hom.)
• Consequence: BTNL3 NM_197975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.297
• Publications: 0 publications found

Genes affected

BTNL3 (HGNC:1143): (butyrophilin like 3) Predicted to enable signaling receptor binding activity. Predicted to be involved in T cell receptor signaling pathway and regulation of cytokine production. Predicted to be integral component of membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299843 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18339676).
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197975.3. 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
	BTNL3	NM_197975.3	MANE Select	c.371A>C	p.Glu124Ala	missense	Exon 2 of 8	NP_932079.1	Q6UXE8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL3	ENST00000342868.7	TSL:1 MANE Select	c.371A>C	p.Glu124Ala	missense	Exon 2 of 8	ENSP00000341787.6	Q6UXE8-1
	BTNL3	ENST00000899564.1		c.371A>C	p.Glu124Ala	missense	Exon 2 of 8	ENSP00000569623.1
	BTNL3	ENST00000946317.1		c.49+4057A>C		intron	N/A	ENSP00000616376.1

Frequencies

GnomAD3 genomes AF: 0.00000731 AC: 1 AN: 136736 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000168

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 4 AN: 194508 AF XY: 0.0000190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.000221

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000245 AC: 32 AN: 1307654 Hom.: 8 Cov.: 31 AF XY: 0.0000323 AC XY: 21 AN XY: 649970

African (AFR) AF: 0.00 AC: 0 AN: 32616

American (AMR) AF: 0.0000804 AC: 3 AN: 37312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24788

East Asian (EAS) AF: 0.00 AC: 0 AN: 35474

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45918

Middle Eastern (MID) AF: 0.00131 AC: 7 AN: 5338

European-Non Finnish (NFE) AF: 0.0000121 AC: 12 AN: 988968

Other (OTH) AF: 0.000164 AC: 9 AN: 54834

GnomAD4 genome AF: 0.00000731 AC: 1 AN: 136736 Hom.: 0 Cov.: 24 AF XY: 0.0000150 AC XY: 1 AN XY: 66464

African (AFR) AF: 0.00 AC: 0 AN: 39738

American (AMR) AF: 0.00 AC: 0 AN: 12928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3332

East Asian (EAS) AF: 0.00 AC: 0 AN: 4680

South Asian (SAS) AF: 0.00 AC: 0 AN: 4582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59692

Other (OTH) AF: 0.00 AC: 0 AN: 1890

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000180 AC: 2

Asia WGS AF: 0.000302 AC: 1 AN: 3326

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	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.30
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.064
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.018	D
Polyphen		0.58	P
Vest4		0.32
MutPred		0.58		Loss of disorder (P = 0.1386)
MVP		0.37
MPC		1.0
ClinPred		0.38	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.24
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs781620493; hg19: chr5-180420134;