chr17-36940736-A-G

Position:

• chr17-36940736-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000614239.1(LHX1):​c.524A>G​(p.Asn175Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LHX1 ENST00000614239.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

Genes affected

LHX1 (HGNC:6593): (LIM homeobox 1) This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for the development of the renal and urogenital systems. This gene is a candidate for Mayer-Rokitansky-Kuster-Hauser syndrome, a disorder characterized by anomalies in the female genital tract. [provided by RefSeq, Dec 2010]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11662671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX1	NM_005568.5	c.524A>G	p.Asn175Ser	missense_variant	3/5	ENST00000614239.1	NP_005559.2
LHX1	XM_047435966.1	c.524A>G	p.Asn175Ser	missense_variant	4/6		XP_047291922.1
LHX1	XM_047435967.1	c.524A>G	p.Asn175Ser	missense_variant	4/6		XP_047291923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX1	ENST00000614239.1	c.524A>G	p.Asn175Ser	missense_variant	3/5	1	NM_005568.5	ENSP00000477829	P1
LHX1	ENST00000616237.1	n.706A>G		non_coding_transcript_exon_variant	3/3	1
	ENST00000614759.1	n.368-511T>C		intron_variant, non_coding_transcript_variant		5
LHX1	ENST00000619939.4	n.1045A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.524A>G (p.N175S) alteration is located in exon 3 (coding exon 3) of the LHX1 gene. This alteration results from a A to G substitution at nucleotide position 524, causing the asparagine (N) at amino acid position 175 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.35	T
Polyphen		0.13	B
Vest4		0.12
MutPred		0.29		Gain of phosphorylation at N175 (P = 0.0218);
MVP		0.32
ClinPred		0.60	D
GERP RS		4.3
Varity_R		0.34
gMVP		0.71

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-35298033;