NM_001144060.2:c.4736C>T

Variant names:

• chr6-138424166-G-A
• rs527299475
• NM_001144060.2:c.4736C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001144060.2(NHSL1):​c.4736C>T​(p.Ala1579Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: NHSL1 NM_001144060.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

Genes affected

NHSL1 (HGNC:21021): (NHS like 1) Predicted to be involved in cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037846267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144060.2. 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
	NHSL1	NM_001144060.2	MANE Select	c.4736C>T	p.Ala1579Val	missense	Exon 8 of 8	NP_001137532.1	Q5SYE7-2
	NHSL1	NM_020464.2		c.4748C>T	p.Ala1583Val	missense	Exon 7 of 7	NP_065197.1	Q5SYE7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHSL1	ENST00000343505.10	TSL:5 MANE Select	c.4736C>T	p.Ala1579Val	missense	Exon 8 of 8	ENSP00000344672.5	Q5SYE7-2
	NHSL1	ENST00000491526.7	TSL:3	c.4967C>T	p.Ala1656Val	missense	Exon 8 of 8	ENSP00000433523.2	H0YDF6
	NHSL1	ENST00000427025.6	TSL:5	c.4748C>T	p.Ala1583Val	missense	Exon 7 of 7	ENSP00000394546.2	Q5SYE7-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152188 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000892 AC: 7 AN: 78438 AF XY: 0.0000993

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000842

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000689 AC: 9 AN: 1306888 Hom.: 0 Cov.: 32 AF XY: 0.00000942 AC XY: 6 AN XY: 637114

African (AFR) AF: 0.00 AC: 0 AN: 28790

American (AMR) AF: 0.00 AC: 0 AN: 22080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19582

East Asian (EAS) AF: 0.000257 AC: 9 AN: 35054

South Asian (SAS) AF: 0.00 AC: 0 AN: 66038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041858

Other (OTH) AF: 0.00 AC: 0 AN: 54272

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152306 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000830 AC: 2

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	0.083
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.086
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.050	T
Polyphen		0.22	B
Vest4		0.060
MutPred		0.055		Loss of glycosylation at S1578 (P = 0.1375)
MVP		0.014
ClinPred		0.077	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.10
Mutation Taster		=100/0	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

dbSNP: rs527299475; hg19: chr6-138745303;