NM_001144060.2:c.4742G>A

Variant names:

• chr6-138424160-C-T
• NM_001144060.2:c.4742G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144060.2(NHSL1):​c.4742G>A​(p.Gly1581Asp) 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NHSL1 NM_001144060.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.374
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073816955).

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.4742G>A	p.Gly1581Asp	missense	Exon 8 of 8	NP_001137532.1	Q5SYE7-2
	NHSL1	NM_020464.2		c.4754G>A	p.Gly1585Asp	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.4742G>A	p.Gly1581Asp	missense	Exon 8 of 8	ENSP00000344672.5	Q5SYE7-2
	NHSL1	ENST00000491526.7	TSL:3	c.4973G>A	p.Gly1658Asp	missense	Exon 8 of 8	ENSP00000433523.2	H0YDF6
	NHSL1	ENST00000427025.6	TSL:5	c.4754G>A	p.Gly1585Asp	missense	Exon 7 of 7	ENSP00000394546.2	Q5SYE7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1300940 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 633394

African (AFR) AF: 0.00 AC: 0 AN: 28560

American (AMR) AF: 0.00 AC: 0 AN: 21078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19288

East Asian (EAS) AF: 0.00 AC: 0 AN: 35030

South Asian (SAS) AF: 0.00 AC: 0 AN: 64962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1039320

Other (OTH) AF: 0.00 AC: 0 AN: 54054

GnomAD4 genome Cov.: 32

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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.2
DANN	Benign	0.39
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.37
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.065		Loss of catalytic residue at G1585 (P = 0.0646)
MVP		0.030
ClinPred		0.074	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.064
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

hg19: chr6-138745297;