NM_178138.6:c.*582G>C

Variant names:

• chr9-136196743-C-G
• rs879304888
• NM_178138.6:c.*582G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178138.6(LHX3):​c.*582G>C variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LHX3 NM_178138.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

LHX3 (HGNC:6595): (LIM homeobox 3) This gene encodes a member of a large family of proteins which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for pituitary development and motor neuron specification. Mutations in this gene cause combined pituitary hormone deficiency 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHX3	NM_178138.6	c.*582G>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000371748.10	NP_835258.1
LHX3	NM_014564.5	c.*582G>C		3_prime_UTR_variant	Exon 6 of 6		NP_055379.1
LHX3	NM_001363746.1	c.*582G>C		3_prime_UTR_variant	Exon 6 of 6		NP_001350675.1
LHX3	XM_017015168.1	c.*582G>C		3_prime_UTR_variant	Exon 6 of 6		XP_016870657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHX3	ENST00000371748	c.*582G>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_178138.6	ENSP00000360813.4
LHX3	ENST00000371746	c.*582G>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000360811.3
LHX3	ENST00000619587	c.*582G>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000483080.1
LHX3	ENST00000645419.1	n.2601G>C		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs879304888; hg19: chr9-139088589;