rs202169457

Variant names:

• chr8-109389083-G-A
• NM_177531.6:c.628G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-109389083-G-A
• chr8-109389083-G-C

Variant summary

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

The NM_177531.6(PKHD1L1):​c.628G>A​(p.Gly210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,590 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G210R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PKHD1L1 NM_177531.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78

Genes affected

PKHD1L1 (HGNC:20313): (PKHD1 like 1) Predicted to act upstream of or within sensory perception of sound. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1L1	NM_177531.6	c.628G>A	p.Gly210Ser	missense_variant	Exon 8 of 78	ENST00000378402.10	NP_803875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1L1	ENST00000378402.10	c.628G>A	p.Gly210Ser	missense_variant	Exon 8 of 78	1	NM_177531.6	ENSP00000367655.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445590 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 719738

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.15
Sift	Benign	0.15	T
Sift4G	Benign	0.062	T
Polyphen		0.84	P
Vest4		0.52
MutPred		0.42		Gain of disorder (P = 0.0715);
MVP		0.30
MPC		0.075
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr8-110401312;