6-138429779-G-C

Variant names:

• chr6-138429779-G-C
• rs148367183
• NM_001144060.2:c.4017C>G

Variant summary

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

The NM_001144060.2(NHSL1):​c.4017C>G​(p.Asp1339Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D1339D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NHSL1 NM_001144060.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023279518).

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.4017C>G	p.Asp1339Glu	missense	Exon 7 of 8	NP_001137532.1	Q5SYE7-2
	NHSL1	NM_020464.2		c.4029C>G	p.Asp1343Glu	missense	Exon 6 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.4017C>G	p.Asp1339Glu	missense	Exon 7 of 8	ENSP00000344672.5	Q5SYE7-2
	NHSL1	ENST00000491526.7	TSL:3	c.4248C>G	p.Asp1416Glu	missense	Exon 7 of 8	ENSP00000433523.2	H0YDF6
	NHSL1	ENST00000427025.6	TSL:5	c.4029C>G	p.Asp1343Glu	missense	Exon 6 of 7	ENSP00000394546.2	Q5SYE7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399436 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690238

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078916

Other (OTH) AF: 0.00 AC: 0 AN: 58040

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.021
DANN	Benign	0.84
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.24	N
PhyloP100		-1.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.093
Sift	Benign	0.56	T
Sift4G	Benign	0.58	T
Polyphen		0.0030	B
Vest4		0.036
MutPred		0.27		Gain of helix (P = 0.0078)
MVP		0.030
ClinPred		0.049	T
GERP RS		-10
Varity_R		0.043
gMVP		0.029
Mutation Taster		=98/2	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: rs148367183; hg19: chr6-138750916;