5-135033862-C-T

Variant names:

• chr5-135033862-C-T
• rs1300560831
• NM_002653.5:c.20G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002653.5(PITX1):​c.20G>A​(p.Gly7Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,329,174 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PITX1 NM_002653.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97

Genes affected

PITX1 (HGNC:9004): (paired like homeodomain 1) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. [provided by RefSeq, Jul 2008]

PITX1-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.20G>A	p.Gly7Asp	missense_variant	Exon 1 of 3	ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.122G>A	p.Gly41Asp	missense_variant	Exon 2 of 4		XP_047273274.1
PITX1-AS1	NR_161235.1	n.267+322C>T		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.20G>A	p.Gly7Asp	missense_variant	Exon 1 of 3	1	NM_002653.5	ENSP00000265340.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000241 AC: 2 AN: 82874 Hom.: 0 AF XY: 0.0000210 AC XY: 1 AN XY: 47566

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 15 AN: 1329174 Hom.: 0 Cov.: 31 AF XY: 0.0000122 AC XY: 8 AN XY: 655782

Gnomad4 AFR exome AF: 0.0000377

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000692

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000851

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;.;T
Eigen	Benign	0.012
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	.;T;T;T
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.8	L;L;.;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Uncertain	0.49
Sift	Benign	0.032	D;D;D;D
Sift4G	Benign	0.29	T;T;.;T
Polyphen		0.67	P;P;.;.
Vest4		0.43
MutPred		0.33		Loss of MoRF binding (P = 0.0125);Loss of MoRF binding (P = 0.0125);Loss of MoRF binding (P = 0.0125);Loss of MoRF binding (P = 0.0125);
MVP		0.91
MPC		2.4
ClinPred		0.44	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.20
gMVP		0.44

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: rs1300560831; hg19: chr5-134369552;