NM_078483.4:c.742C>A

Variant names:

• chr5-151473691-C-A
• NM_078483.4:c.742C>A

Variant summary

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

The NM_078483.4(SLC36A1):​c.742C>A​(p.His248Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC36A1 NM_078483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.01
• Publications: 0 publications found

Genes affected

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

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=0.016411513).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078483.4. 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
	SLC36A1	NM_078483.4	MANE Select	c.742C>A	p.His248Asn	missense	Exon 8 of 11	NP_510968.2
	SLC36A1	NM_001349740.2		c.658C>A	p.His220Asn	missense	Exon 9 of 12	NP_001336669.1
	SLC36A1	NM_001308150.2		c.742C>A	p.His248Asn	missense	Exon 8 of 11	NP_001295079.1	Q7Z2H8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC36A1	ENST00000243389.8	TSL:1 MANE Select	c.742C>A	p.His248Asn	missense	Exon 8 of 11	ENSP00000243389.3	Q7Z2H8-1
	SLC36A1	ENST00000521925.5	TSL:1	c.742C>A	p.His248Asn	missense	Exon 8 of 10	ENSP00000430305.1	E7EW39
	SLC36A1	ENST00000520701.5	TSL:5	c.742C>A	p.His248Asn	missense	Exon 8 of 11	ENSP00000428140.1	Q7Z2H8-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.058
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.23
DANN	Benign	0.71
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.023	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.50	N
PhyloP100		-1.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.33		Loss of sheet (P = 0.1158)
MVP		0.15
MPC		0.32
ClinPred		0.023	T
GERP RS		-2.3
PromoterAI		0.0066	Neutral
Varity_R		0.048
gMVP		0.34
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr5-150853252;